THE GOLD STANDARD IN LUNG PRESERVATION
Perfadex® is a lightly buffered ‘extracellular’, (low [K+]) colloid-based electrolyte preservation solution for rapid cooling, perfusion and storage of organs in connection with transplantation.
Perfadex® – A solution for optimal preservation of donor lungs
The composition of Perfadex® has been specifically formulated to preserve the function and integrity of organs rich in endothelium, during flushing and cold ischemic storage, prior to transplantation and reperfusion. The colloid component, dextran 40, particularly protects the microvasculature against post-ischemic reperfusion injury, primarily by preventing pathological leukocyte-endothelial interaction.12,13 It also prevents edema formation during preservation.
Numerous studies have shown that Perfadex® enable safe preservation of lungs up to between 4 and 12 hours, depending of status of the organ during retrieval.
The colloid component, dextran 40, particularly protects the microvasculature against post-ischemic reperfusion injury, primarily by preventing pathological leukocyte endothelial interaction.
THE ENDOTHELIUM – A VULNERABLE TISSUE
The lung is primarily composed of endothelial cells which line the enormous surface area of the capillaries (equivalent to an entire tennis court) and a similar surface area of types I and II epithelial cells which line the alveoli and secrete surfactant respectively. The endothelium is the most vulnerable and plays a critical role for the structure and function of a normal vessel wall. Endothelial cells produce a variety of biologically active substances that control vascular permeability, vessel tone, coagulation, fibrinolysis and inflammatory responses. Some of these substances, such as proteins which seal the junctions between cells (adhesion molecules), are integral parts of the cell structure. Others, such as nitric oxide (NO), prostacycline, chemokines, or factors involved in coagulation and fibrinolysis, are produced and then released by the endothelial cells either luminally or abluminally.
WHAT CAUSES DAMAGE TO THE ENDOTHELIUM?
A number of factors can injure the pulmonary endothelium during the manipulation and temporary storage involved in the harvesting of donor lungs;
- Traumatic manipulation during harvesting, evaluation and transplantation
- Excessive pressure
- Low temperature – particularly below 2 ⁰C
- Storage solution – e.g. intracellular type (high K+) solutions
- Prolonged cold ischemia
- Ischemia-reperfusion – free radical injury
Consequences of an injured endothelium
Injured endothelium can induce platelet and leukocyte sticking which then triggers a number of inflammatory cascades including increased permeability of the capillary wall, which in turn increases tissue edema and the risk of Primary Graft Dysfunction (PGD).
A well preserved endothelium is antithrombogenic, yet promotes platelet aggregation and coagulation if injured.
The importance of an intact endothelium
Experimental and clinical evidence indicates that early ischemia-reperfusion injury to the endothelium, within the very first few hours of reperfusion, is a key trigger in initiating the cytokine cascades which eventually lead to PGD and subsequent graft failure often months or years later. This early injury can be prevented or mitigated by minimizing physical injury (manipulation) and storing the lungs in a protective solution under optimal temperature conditions.
CURRENT BEST PRACTICE
Current best practice based on the latest research on intensive-care management of potential lung donor and lung-preservation techniques are summarized below.
Lung preservation techniques
- Extracellular solution consisting of dextran-40, glucose and low potassium
- Anterograde and retrograde flushing of 60 mL/kg and max 30 cm height
- Storage temperature 2-8 ⁰C
- Inflation to 50% of total lung capacity, fraction of inspired oxygen 50%
- Pharmacological additives: prostaglandin E1, heparin, glucocorticoids
- Cold ischemic times generally less than 8 h
- Normothermic ex-vivo lung perfusion based on lung assessment and therapeutics
Table modified from “Donor management and lung preservation for lung transplantation”.
Perfadex® should be cooled to 2-8 ⁰C (36-46 ⁰F). Adjust to about pH 7.4 shortly before use by addition of 1 mmol THAM/TRIS (trometamol or tromethamine) per litre Perfadex®.
Once additives have been administered or the container has been opened the solution should be kept chilled and used within 24 hours.
Perfadex® is supplied in 1000 mL or 2800 mL (PVC bags)
In USA Perfadex® is supplied with THAM
REF 19001; 8 x 1000 mL, REF 19002; 2 x 2800 mL, REF 19017*; 8 x 1000 mL, REF 19018*; 2 x 2800 mL
*REF number used in the USA including THAM bottle **
19001: 8 x 1000 ml bags with Perfadex®
19002: 2 x 2800 ml bags with Perfadex®
19017: 8 x 1000 ml bags with Perfadex®, 1 bottle with THAM 50 ml, 3.3 mmol/ml
19018: 2 x 2800 ml bags with Perfadex®, 1 bottle with THAM 50 ml, 3.3 mmol/ml
19001: 1000 ml PVC bags
19002: 2800 ml PVC bags
19017: 1000 ml PVC bags
19018: 2800 ml PVC bags
Storage: Store at room temperature. Do not freeze. Ensure that the bag is not in direct contact with ice. Use only unopened and undamaged packages.
Shelf life: At least six months from date of shipment.
Intended Use: Perfadex® solution for lung perfusion is indicated for the flushing, storage and transportation of isolated lungs after removal from the donor in preparation for eventual transplantation into a recipient.
**THAM is a biological buffer used to adjust pH of Perfadex®